Bioconjugate Chemistry, Год журнала: 2024, Номер 35(9), С. 1429 - 1440

Опубликована: Авг. 19, 2024

Drug delivery to the esophagus through systemic administration remains challenging, as minimal drug reaches desired target. Local offers potential for improved efficacy while minimizing off-target toxicities but necessitates bioadhesive properties mucosal delivery. Herein, we describe synthesis of two new mucoadhesive amphiphilic copolymers prepared by sequential ring-opening copolymerization or postpolymerization click conjugation. Both strategies yield block containing a hydrophilic amine-functionalized poly-amido-saccharide and either hydrophobic alkyl derivatized poly(lactic acid), respectively. The latter resulting readily self-assemble into spherical, ≈200 nm diameter, positively charged nanoparticles. NPs entrap ultrahigh levels paclitaxel via encapsulation free conjugated biodegradable, biocompatible poly(1,2-glycerol carbonate). Paclitaxel-loaded rapidly enter cells, release paclitaxel, are cytotoxic esophageal OE33 OE19 tumor cells in vitro, and, importantly, demonstrate mucoadhesion compared conventional poly(ethylene glycol)-poly(lactic acid) nanoparticles ex vivo tissue.

Язык: Английский